Bibliometric analysis of myelin imaging studies of patients with multiple sclerosis (2000-2022).

Background: Multiple sclerosis (MS) is a condition that can impact the central nervous system (CNS) and cause damage to the myelin, which is responsible for facilitating the normal transmission of electrical impulses along the nerves. We performed a bibliometric analysis of the scientific publications on myelin imaging in MS to reveal the development trends in this field and to evaluate research trends in myelin imaging in MS. Methods: The Web of Science Core Collection was searched for articles related to myelin imaging in MS published between January 2000 and December 2022. CiteSpace, VOSviewer, and R language were used to evaluate and visualize contributions by and co-occurrence relationships among countries and institutions, authors, journals, citations, keywords, and so on. Results: A total of 1,639 articles addressed the topic of myelin imaging in MS. The United States had the largest number of annual publications. The University of London was the institution with the highest number of publications (n=118) and citations (n=9,885). The top 3 productive authors were all from the University of British Columbia in Canada. An article published by Mackay et al. in 1994 had the most citations (n=272). Neuroimage [impact factor (IF) =7.40, Journal Citation Reports quartile 1 (Q1)] was the most productive journal in terms of the number of articles relating to myelin imaging in MS (n=149). In recent years, myelin water imaging, synthetic magnetic resonance imaging (SyMRI), inhomogeneous magnetization, positron emission tomography (PET) imaging, and aquaporin-4 (AQP4) have been researched hotspots of myelin imaging in MS. Conclusions: With advancements in the pathophysiological research on myelin changes in MS, myelin imaging is playing an important role in the diagnosis and treatment of MS. In addition, the use of new sequences of myelin imaging to distinguish MS from other inflammatory demyelinating diseases is a future development trend in this field.

Therapeutic Effects of Perilla Phenols in Oral Squamous Cell Carcinoma.

The herbal medicine perilla leaf extract (PLE) exhibits various pharmacological properties. We showed that PLE inhibits the viability of oral squamous cell carcinoma (OSCC) cells. HPLC analysis revealed that caffeic acid (CA) and rosmarinic acid (RA) are the two main phenols in PLE, and reduced OSCC cell viability in a dose-dependent manner. The optimal CA/RA combination ratio was 1:2 at concentrations of 300-500 µM but had no synergistic inhibitory effect on the viability of OSCC cells. CA, RA, or their combination effectively suppressed interleukin (IL)-1ß secretion by OSCC OC3 cells. Long-term treatment with CA and CA/RA mixtures, respectively, induced EGFR activation, which might cause OC3 cells to become EGFR-dependent and consequently increased the sensitivity of OC3 cells to a low dose (5 µM) of the EGFR tyrosine kinase inhibitor gefitinib. Chronic treatment with CA, RA, or their combination exhibited an inhibitory effect more potent than that of low-dose (1 µM) cisplatin on the colony formation ability of OSCC cells; this may be attributed to the induction of apoptosis by these treatments. These findings suggest that perilla phenols, particularly CA and RA, can be used as adjuvant therapies to improve the efficacy of chemotherapy and EGFR-targeted therapy in OSCC.

Abnormal dynamic functional connectivity of thalamic subregions in patients with first-episode, drug-naïve major depressive disorder.

Background: Recent studies have shown that major depressive disorder (MDD) is associated with altered intrinsic functional connectivity (FC) of the thalamus; however, investigations of these alterations at a finer time scale and the level of thalamic subregions are still lacking. Methods: We collected resting-state functional MRI data from 100 treatment-naïve, first-episode MDD patients and 99 age-, gender- and education-matched healthy controls (HCs). Seed-based whole-brain sliding window-based dFC analyses were performed for 16 thalamic subregions. Between-group differences in the mean and variance of dFC were determined using threshold-free cluster enhancement algorithm. For significant alterations, there relationships with clinical and neuropsychological variables were further examined via bivariate and multivariate correlation analyses. Results: Of all thalamic subregions, only the left sensory thalamus (Stha) showed altered variance of dFC in the patients characterized by increases with the left inferior parietal lobule, left superior frontal gyrus, left inferior temporal gyrus, and left precuneus, and decreases with multiple frontal, temporal, parietal, and subcortical regions. These alterations accounted for, to a great extent, clinical, and neuropsychological characteristics of the patients as revealed by the multivariate correlation analysis. In addition, the bivariate correlation analysis revealed a positive correlation between the variance of dFC between the left Stha and right inferior temporal gurus/fusiform and childhood trauma questionnaires scores (r = 0.562, P < 0.001). Conclusion: These findings suggest that the left Stha is the most vulnerable thalamic subregion to MDD, whose dFC alterations may serve as potential biomarkers for the diagnosis of the disease.

Atypical imaging features of the primary spinal cord glioblastoma: A case report.

BACKGROUND: Primary spinal cord (PSC) glioblastoma (GB) is an extremely rare but fatal primary tumor of the central nervous system and associated with a poor prognosis. While typical tumor imaging features are generally easy to recognize, glioblastoma multiforme can have a wide range of imaging findings. Atypical GB is often misdiagnosed, which usually delays the optimal time for treatment. In this article, we discuss a clinical case of pathologically confirmed PSC GB under the guise of benign tumor imaging findings, as well as the most recent literature pertaining to PSC GB. CASE SUMMARY: A 70-year-old female complained of limb weakness lasting more than 20 d. Irregular masses were observed inside and outside the left foramina of the spinal canal at C7-T1 on medical imaging. Based on the imaging features, radiologists diagnosed the patient with schwannoma. Tumor resection was performed under general anesthesia. The final histopathological findings revealed a final diagnosis of PSC GB, world health organization Grade IV. The patient subsequently underwent a 4-wk course of radiotherapy (60 Gy in 20 fractions) combined with temozolomide chemotherapy. The patient was alive at the time of submission of this manuscript. CONCLUSION: Atypical GB presented unusual imaging findings, which led to misdiagnosis. Therefore, a complete recognition of imaging signs may facilitate early accurate diagnosis.

Subregion-specific, modality-dependent and timescale-sensitive hippocampal connectivity alterations in patients with first-episode, drug-naïve major depression disorder.

BACKGROUND: Despite accumulating evidence for the hippocampus as a key dysfunctional node in major depressive disorder (MDD), previous findings are controversial possibly due to heterogeneous and small clinical samples, complicated hippocampal structure, and different imaging modalities and analytical methods. METHODS: We collected structural and resting-state functional MRI data from 100 first-episode, drug-naïve MDD patients and 99 healthy controls. A subset of the participants (34 patients and 33 controls) also completed a battery of neuropsychological tests and childhood trauma questionnaires. Seed-based morphological and functional (static and dynamic) connectivity were calculated for ten hippocampal subregions, followed by analyses of dynamic functional connectivity states (k-means clustering), connectivity cross-modality relationships (cosine similarity), and connectivity associations with clinical and neuropsychological variables (Spearman correlation). RESULTS: Between-group comparisons revealed abnormal hippocampal connectivity in the patients that depended on 1) hippocampal subdivisions: the cornu ammonis (CA) was the most seriously affected subregion, in particular the right CA1 for functional connectivity alterations; 2) imaging modality: morphological connectivity revealed seldom and sporadic alterations with different lobes, while functional connectivity identified numerous and convergent alterations with prefrontal regions; and 3) time scale: dynamic functional connectivity was more sensitive than static functional connectivity, in particular in revealing alterations between the right CA1 and contralateral prefrontal cortex. Among the 34 patients, functional connectivity alterations of the CA1 were related to the history of childhood trauma in the patients. LIMITATIONS: Only a subset of the patients completed the neuropsychological tests, which may cause underestimation of cognitive relevance of hippocampal connectivity alterations. CONCLUSIONS: Disrupted hippocampal CA1 functional connectivity plays key roles in the pathophysiology of MDD and may act as a potential diagnostic biomarker for the disease.

Abnormal Functional Connectivity of Posterior Cingulate Cortex Correlates With Phonemic Verbal Fluency Deficits in Major Depressive Disorder.

Background: Major depressive disorder (MDD) patients face an increased risk of developing cognitive impairments. One of the prominent cognitive impairments in MDD patients is verbal fluency deficit. Nonetheless, it is not clear which vulnerable brain region in MDD is interactively linked to verbal fluency deficit. It is important to gain an improved understanding for verbal fluency deficit in MDD. Methods: Thirty-four MDD patients and 34 normal controls (NCs) completed resting-state fMRI (rs-fMRI) scan and a set of verbal fluency tests (semantic VFT and phonemic VFT). Fourteen brain regions from five brain networks/systems (central executive network, default mode network, salience network, limbic system, cerebellum) based on their vital role in MDD neuropathology were selected as seeds for functional connectivity (FC) analyses with the voxels in the whole brain. Finally, correlations between the z-score of the FCs from clusters showing significant between-group difference and z-score of the VFTs were calculated using Pearson correlation analyses. Results: Increased FCs in MDD patients vs. NCs were identified between the bilateral posterior cingulate cortex (PCC) and the right inferior frontal gyrus (triangular part), in which the increased FC between the right PCC and the right inferior frontal gyrus (triangular part) was positively correlated with the z score of phonemic VFT in the MDD patients. Moreover, decreased FCs were identified between the right hippocampal gyrus and PCC, as well as left cerebellum Crus II and right parahippocampal gyrus in MDD patients vs. NCs. Conclusions: The MDD patients have altered FCs among key brain regions in the default mode network, the central executive network, the limbic system, and the cerebellum. The increased FC between the right PCC and the right inferior frontal gyrus (triangular part) may be useful to better characterize pathophysiology of MDD and functional correlates of the phonemic verbal fluency deficit in MDD.

Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder.

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. The model estimates the directed connection strengths between different neural populations both within and between brain regions based on resting-state fMRI data collected from normal healthy subjects and patients with MDD. Results show that MDD is primarily characterized by abnormal circuit interactions in the EXE-LIM network rather than the DMN-SAL network. Specifically, we observe reduced frontoparietal effective connectivity that potentially contributes to hypoactivity in the dorsolateral prefrontal cortex (dlPFC), and decreased intrinsic inhibition combined with increased excitation from the superior parietal cortex (SPC) that potentially lead to amygdala hyperactivity, together resulting in activation imbalance in the PFC-amygdala circuit that pervades in MDD. Moreover, the model reveals reduced PFC-to-hippocampus excitation but decreased SPC-to-thalamus inhibition in MDD population that potentially lead to hypoactivity in the hippocampus and hyperactivity in the thalamus, consistent with previous experimental data. Overall, our findings provide strong support for the long-standing limbic-cortical dysregulation model in major depression but also offer novel insights into the multiscale pathophysiology of this debilitating disease.

Clinical application value of Inhibin B alone or in combination with other hormone indicators in subfertile men with different spermatogenesis status: A study of 324 Chinese men.

BACKGROUND: In this study, we investigated the clinical value of serum Inhibin B alone or in combination with other hormone indicators in subfertile men. METHODS: This is a multicenter study involving 324 men from different cities in China. Testicular volume, routine semen analysis, serum Inhibin B, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and prolactin were measured. Testicular tissue samples were also analyzed in 78 of 129 patients with azoospermia to distinguish impaired spermatogenesis from obstructive azoospermia. RESULTS: The concentration of Inhibin B, FSH, and AMH is related to spermatogenesis. For men with impaired spermatogenesis, including mild-to-moderate oligozoospermia (IMO) and severe oligozoospermia (ISO), serum levels of Inhibin B and FSH are highly correlated with sperm counting. However, in patients with idiopathic moderate oligozoospermia or severe oligozoospermia, there was no significant correlation between Inhibin B (or FSH) and sperm concentration. The upper cutoff value of Inhibin B to diagnose ISO is 58.25 pg/ml with a predictive accuracy of 80.65%. To distinguish between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA), the area under the curve (AUC) for AMH + Inhibin B + FSH is very similar to Inhibin B (0.943 vs. 0.941). The cutoff level of Inhibin B to diagnose nonobstructive azoospermia is 45.9 pg/ml with a positive and negative prediction accuracy of 97.70% and 85.71%, respectively. CONCLUSION: In summary, Inhibin B is a promising biomarker alone or in combination with other hormone indicators for the diagnosis of testicular spermatogenesis status, helping clinical doctors to distinguish NOA from OA.

Decreased testosterone secretion index and free testosterone level with multiple symptoms for late-onset hypogonadism identification: a nationwide multicenter study with 5980 aging males in China.

Late-onset hypogonadism (LOH) is a syndrome in middle-aged and elderly men caused by age-related testosterone deficiency. Age-related change of total testosterone (TT) of Asian males is different from Caucasian population, suggesting difference for LOH identification in Asians. A nationwide cross-sectional study involving six centers in China was conducted. Totally 6296 men aged 40-79 were recruited. After exclusions 5980 men were left for analyses. The serum TT level, was neither decreased with aging nor correlated with most hypogonadal symptoms. Instead, ten hypogonadal symptoms were found to be significantly correlated with free testosterone and testosterone secretion index, thus were chosen to form a concise scale. Further analysis identified a level of free testosterone <210 pmol/L, testosterone secretion index <1.8, and the concise scale score ≧17 could be diagnosed as having significantly aggravated LOH. This study developed an evidence-based criteria for LOH identification in Chinese population and may be adopted in other Asians. It includes the impaired testosterone secretion ability and deficiency of bioavailable testosterone, which should be the main cause in LOH pathogenesis despite normal TT levels, as well as correlated multiple hypogonadal symptoms. Our results may guide the LOH treatment to increase testicular function of testosterone secretion and bioavailable testosterone.

Altered Resting-State Functional Connectivity of Multiple Networks and Disrupted Correlation With Executive Function in Major Depressive Disorder.

Background: Major depressive disorder (MDD) is one of the most common and costly psychiatric disorders. In addition to significant changes in mood, MDD patients face an increased risk of developing cognitive dysfunction. It is important to gain an improved understanding of cognitive impairments and find a biomarker for cognitive impairment diagnosis in MDD. Methods: One hundred MDD patients and 100 normal controls (NCs) completed resting-state fMRI (rs-fMRI) scan, in which 34 MDD patients and 34 NCs had scores in multiple cognitive domains (executive function, verbal fluency, and processing speed). Twenty-seven regions of interest from the default mode network (DMN), central executive network (CEN), salience network (SN), and limbic system (LS) were selected as seeds for functional connectivity (FC) analyses with the voxels in the whole brain. Finally, partial correlations were conducted for cognitive domain scores and FCs with significant differences between the MDD and NC groups. Results: Significant FC differences between groups were identified among the seeds and clusters in the DMN, CEN, LS, visual network, somatomotor network, ventral attention network, and dorsal attention network. In the MDD patients, the magnitude of the Stroop interference effect was positively correlated with the illness duration, and the illness duration was negatively correlated with the FC between the right ventral hippocampal gyrus and the left inferior frontal gyrus. However, the correlation between the Stroop interference effect and the FC of the right anterior prefrontal cortex with the left cerebellum_4_5 was disrupted in these patients. Conclusions: The MDD patients have altered FCs among multiple brain networks and a disrupted correlation between the FC of prefrontal cortex and executive function. The disrupted correlation could present before the symptoms develop and may be the core process in the development of executive function impairment.

Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task-based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within-network or between-network connectivities, we applied spectral dynamic causal modeling to estimate EC of a large-scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), based on large sample-size resting-state fMRI consisting of 100 healthy subjects and 100 individuals with first-episode drug-naive MDD. We applied a newly developed parametric empirical Bayes (PEB) framework to test specific hypotheses. We showed that MDD altered EC both within and between high-order functional networks. Specifically, MDD is associated with reduced excitatory connectivity mainly within the default mode network (DMN), and between the default mode and salience networks. In addition, the network-averaged inhibitory EC within the DMN was found to be significantly elevated in the MDD. The coexistence of the reduced excitatory but increased inhibitory causal connections within the DMNs may underlie disrupted self-recognition and emotional control in MDD. Overall, this study emphasizes that MDD could be associated with altered causal interactions among high-order brain functional networks.

Long-term safety, health and mental status in men with vasectomy.

Vasectomy is an efficient male contraceptive method, but the long-term effects of this technology in a large population are unclear. To investigate the influence of vasectomy on long-term health effects, we recruited 485 men with a vasectomy and 1940 men without vasectomy in China. After obtaining basic information from the Aging Males' Symptoms (AMS) scale and other questionnaires, peripheral blood was drawn to assess the hormone levels, prostate specific antigen (PSA) and blood biochemistry. Using multiple linear regression analysis, these factors had no relationship with vasectomy except for four factors including the Somatic score (0.31, 0.02 and 0.61) in AMS, SF-36 score (-18.8, -32.00 and -5.60), "Role emotional" (-6.28, -10.34 and -2.22) and "Mental health" (-1.55, -3.08 and -0.02). A stratified analysis showed that with increased age, smoking and drinking, residence in township or a higher level of education, the mental health of men was worse. Vasectomy had no long-term effect on the level of sexual hormones in men, and it did not increase the level of PSA. The impact of the vasectomy on quality of life in men were mainly reflected in psychological effects, which suggests that men with vasectomy groups many benefit from professional psychological counseling.

The plasma miR-125a, miR-361 and miR-133a are promising novel biomarkers for Late-Onset Hypogonadism.

Circulating miRNAs have been shown to serve as diagnostic/prognostic biomarkers in cancers and other diseases. However, the role of plasma miRNAs in Late-onset hypogonadism (LOH) diagnosis is still unknown. Using Illumina HiSeq2000 sequencing at discovery phase, and then two-step validated by reverse transcriptase polymerase chain reaction (RT-PCR) assays in verification phases. We verified that the expression levels of miR-125a-5p, miR-361-5p and miR-133a-3p were significantly altered in LOH group compared to the control group. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.682, 0.698 and 0.765, respectively. The combination of three miRNAs showed a larger AUC (0.835) that was more efficient for the diagnosis of LOH. Among three miRNAs, miR-133a-3p had the best diagnostic value for LOH with 68.2% sensitivity and 77.3% specificity. Regression analyses show that miR-133a-3p level was negatively associated with the ageing males' symptoms (AMS) scale. However, miR-361-5p level was positively associated with serum testosterone concentrations. In summary, plasma miRNAs are differentially expressed between LOH and healthy controls. We validated three miRNAs that could act as novel biomarkers for diagnosis of LOH. These miRNAs may be involved in the development of LOH. However, further large and functional studies are warranted to confirm our findings.

miR-424/322 is downregulated in the semen of patients with severe DNA damage and may regulate sperm DNA damage.

Sperm DNA integrity is an essential factor for accurate transmission of genetic information. Human sperm DNA damage is a common cause of male infertility but the exact mechanism remains poorly understood. Considering the vital role of microRNA (miRNA) in multiple pathophysiological processes, we hypothesised that testicular miRNA is involved in sperm DNA damage during spermatogenesis. Infertile patients with high sperm DNA fragment index (DFI; n=94) were selected from 1090 infertile men and a total of 18 testis-specific seminal miRNAs previously identified from human seminal plasma were chosen and tested. miR-29c and miR-424 were downregulated in men with high DFI. The inhibition of these two miRNAs in mice confirmed the role of miR-424 (murine homologue miR-322) in sperm DNA damage during spermatogenesis; by contrast, miR-29c exhibited a negative result. Thus, miR-424/322 is involved in sperm DNA damage. Furthermore, the dysregulation of this miRNA can induce DNA double-strand breaks during spermatogenesis.

Performance of a half-saturated vertical flow wetland packed with volcanic gravel in stormwater treatment.

A half-saturated pilot-scale wetland planted with Acorus calamus was built to treat urban stormwater. The design comprises a sedimentation tank for pretreatment, and a vertical flow volcanic gravel wetland bed equipped with a recirculation device. Eighteen rainfall events were monitored in 2012. The treatment system achieved total removal efficiencies of 99.4, 81, 50, and 86% for suspended solids, organic matter, nitrogen and phosphorus, respectively, and 29, 68, and 25% for copper, zinc, and lead, respectively, at a 3-day hydraulic residence time. In the wetland bed, the removal of ammonia, total nitrogen, and zinc were improved by recirculation. Plant uptake provided 18% of nitrogen removal and 39% of phosphorus removal. During the experimental stage, only 1.4% of the pore volume in substrate was reduced due to clogging, implying that the wetland can operate without clogging for a relatively long period.

Particle retention in compact constructed wetlands treating highway stormwater.

Three pilot-scale compact constructed wetland systems were constructed to treat stormwater from a highway. They each comprised a sedimentation tank, and a vertical flow (VF) wetland bed equipped with a recirculation device. The VF wetland beds were filled with woodchip, pumice and volcanic gravel, respectively. According to the analysis of the particle size distributions (0.52-500 µm), the predominant particles in stormwater ranged in size from 0.52-30 µm. In the sedimentation tank, with a 24 h settling time, the settling efficiencies of the particles increased with increasing particle size. In the VF wetland beds, further capture of the particles was achieved; however, the woodchip and volcanic gravel wetlands displayed relatively low trapping of micro-particles, due to the natural properties of the substrates. Recirculation caused a positive effect on the retention of particles in the woodchip wetland. Due to the employment of a pre-treatment tank and the high porosity of materials, the accumulated solids occupied very low proportions of the pore volume in the wetland substrates. The results also showed that the accumulation of copper, zinc and lead do not pose a problem for the disposal of the substrates when the wetlands reach the end of their operational lifetime.

Performance of a vertical subsurface flow (VSF) wetland treatment system using woodchips to treat livestock stormwater.

This study was conducted to develop a vertical subsurface flow (VSF) wetland remediation system packed with woodchips to control stormwater pollution arising from livestock agriculture. Three lab-scale VSF wetlands were operated with recirculation during the interval (Δ) between storms as 2, 4 and 8 days, respectively. The fed water was 100% recirculated one time per 24 h; the recirculation frequency was 1, 3 and 7 times at Δ of 2, 4 and 8 days, respectively. The constructed wetland systems proved to be effective in reducing total suspended solid (TSS), but also had potential for increasing TSS in the effluent due to the properties of the woodchips. The release of organic matter, especially in the dissolved form, occurred during the initial 60 days. The removal efficiencies of total nitrogen (TN) were 26.2%, 34.1% and 50.0% at Δ of 2, 4 and 8 days, respectively. Nitrification was promoted by the abundant oxygen supplied when the water in wetland was recirculated and fed into the wetland. Denitrification was stable and effective due to the availability of carbon sources. The influent total phosphorus (TP) was reduced from an average of 2.05 mg L(-1) to 1.79 mg L(-1), 1.36 mg L(-1) and 0.86 mg L(-1) at Δ as 2, 4 and 8 days, respectively. The result shows that woodchips can be used as substrate material for VSF wetland treatment systems to control nutrient influx from livestock stormwater.